MODY Diabetes

Maturity-onset diabetes of the young (MODY) is a non-insulin-dependent type of diabetes mellitus that doctors usually discover in young adults. MODY is mostly an autosomal dominant condition, separated into subgroups (MODY1 to MODY14) based on the genetic mutation that causes the disease. Roughly 95%¹ of all MODY instances are caused by mutations in three genes (HNF1A, HNF4A, and GCK). Moreover, doctors should suspect MODY in non-obese patients who were diagnosed with diabetes at a young age (younger than 30 years) and have a strong family history of diabetes. It is frequently misunderstood as type 1 or type 2 diabetes.² MODY (Maturity-Onset Diabetes of the Young) is a form of monogenic diabetes, distinct from polygenic forms like type 1 and type 2 diabetes.

What is the Cause Of MODY Diabetes?

MODY (Maturity-Onset Diabetes of the Young) is caused by genetic mutations that impair the ability of pancreatic beta cells to detect blood sugar changes and produce sufficient insulin. This condition is primarily linked to mutations in specific genes, such as HNF1A, HNF4A, and GCK, which account for the majority of MODY cases. It follows an autosomal dominant inheritance pattern, meaning a child has a 50% chance of inheriting the condition if one parent carries the mutation. Although most cases of MODY are familial, it can also arise from new (de novo) mutations. Symptoms typically develop before the age of 25, independent of environmental factors. While rare, MODY has been linked to approximately 20 genes, underscoring its genetic complexity.³

MODY Diabetes Symptoms

MODY (Maturity-Onset Diabetes of the Young) typically has a gradual onset, and symptoms may go unnoticed for years. Common symptoms include frequent urination, increased thirst, blurry vision, fatigue, and recurrent skin or yeast infections. These symptoms are usually mild compared to other forms of diabetes.⁴

Clinical Features of MODY:

It usually manifests before the age of 25.
It follows an autosomal dominant inheritance pattern, often appearing across multiple generations in a family.
Unlike type 1 diabetes, insulin therapy is often unnecessary; management typically involves dietary changes or oral medications.
People with MODY generally maintain a healthy weight, as obesity is not a common factor in this condition.

4 Most Common MODY Diabetes Types

HNF1-Alpha Gene:

MODY 3 is the most common form of MODY, caused by mutations in the HNF1-alpha gene. This mutation impairs beta-cell growth and reduces insulin production. Diabetes typically develops during adolescence or early adulthood. Treatment usually involves low-dose sulphonylureas, which enhance insulin release. Insulin is rarely needed unless the condition progresses.⁵⁶

HNF4-Alpha Gene:

Mutations in the HNF4-alpha gene cause MODY 1, a less common form of MODY. Affected individuals may present with high birth weight and low blood sugar levels at birth. Sulphonylureas are the first line of treatment, though insulin may be required later in life as the disease progresses.⁷

HNF1-Beta Gene:

MODY 5, caused by HNF1-beta mutations, often involves kidney abnormalities, such as cysts, alongside diabetes. These kidney issues may be detectable prenatally. Diabetes usually develops later in life and often requires insulin therapy. The condition may also affect other organs, including the liver and reproductive system.

GCK Gene:

MODY 2, caused by GCK mutations, leads to mild, persistent hyperglycemia that is often asymptomatic. Blood glucose levels typically range between 5.8 and 8.3 mmol/L. This form of MODY does not require treatment and is often identified incidentally, such as during routine screenings in pregnancy.⁸

For all MODY types except MODY 2, there is a potential risk of long-term complications if blood sugar is not well managed. A balanced diet, regular exercise, and maintaining healthy blood sugar and cholesterol levels can help mitigate this risk.

How Is It Diagnosed?

MODY is diagnosed through a combination of medical history, physical examinations, and laboratory tests, including blood glucose, HbA1c, insulin levels, pancreatic function tests, and genetic testing. Distinguishing MODY from other diabetes types is crucial for ensuring appropriate treatment. Testing for MODY is important as many forms may lack visible symptoms. If routine blood tests reveal elevated blood sugar levels, further investigation is warranted. Genetic testing is the definitive diagnostic tool for MODY and is recommended for individuals with the following characteristics:

Onset of diabetes before age 25.
A strong family history of diabetes spanning generations.
Evidence of insulin production, as shown by normal C-peptide levels.⁹
Negative results for beta-cell autoantibodies.

MODY Diabetes Treatment

There is no known treatment for MODY, as it is a disease caused by hereditary mutations. However, gaining a precise analysis can initiate the management of MODY.

Lifestyle Modification

The treatment of Maturity-Onset Diabetes of the Young (MODY) highly depends on the specific genetic type. The first goal of treatment for MODY is to prevent hypoglycemia and maintain blood sugar levels within a normal range. Moreover, lifestyle modifications such as maintaining a healthy body weight, regular exercise, and a low-carb diet are the first few steps towards managing MODY and improving the overall quality of life.¹⁰

Regular Monitoring

Diet and lifestyle changes play one of the most important roles in managing MODY. A suitable management plan for these individuals is to put them on a low carbohydrate diet when they are first investigated with the disease and their blood glucose and glycated hemoglobin (HbA1c) levels are still within the “non-diabetic” range. Since they are likely to experience significant hyperglycemia following oral glucose load, these individuals may benefit from a low-carbohydrate diet that lowers postprandial blood glucose levels.
Therefore, regular monitoring of blood glucose levels and glycated hemoglobin (HbA1c) is necessary to evaluate treatment efficiency and make necessary adjustments if needed.

Image of a glucometer to monitor MODY diabetes

Insulin Therapy

In some cases, people with MODY may require insulin therapy to control elevated blood sugar levels. Additionally, a class of drugs known as oral sulfonylureas and DPP-4 inhibitors can treat insulin sensitivity and provoke insulin production.
Healthcare providers should modify the treatment approach for MODY and tailor it to each patient’s unique needs. Genetic testing should be done to determine the specific subtype of MODY because it helps inform the most appropriate treatment approach for each individual. Regular follow-up appointments, along with regular monitoring of blood glucose levels and adherence to lifestyle changes and medication regimens, are essential in effectively managing MODY diabetes.

How Common is MODY Diabetes?

MODY is a rare form of diabetes that accounts for almost about 1-2% of all cases of diabetes. A genetic change causes it, and one or both parents pass it down. About 5% of diabetes cases in the United States are MODY.¹¹

What are the Risk Factors of MODY?

Risk factors for MODY include a strong family history related to the condition. Other risk factors may include lack of insulin resistance, young age of onset, history of pancreatic disorders, or other diabetes-related complications.

Can MODY Diabetes be Prevented?

Since a genetic alteration causes it, one cannot prevent it. However, knowing one’s history and undergoing genetic testing can help them manage it adequately through lifestyle modifications and appropriate medical treatment.

Conclusion

Maturity-Onset Diabetes of the Young (MODY) is a rare form of diabetes that genetic causes characterize, and it typically occurs before the age of 25. Specific gene mutations affecting the production and functioning of insulin cause MODY, distinguishing it from Type 1 or Type 2 diabetes. MODY diabetes often follows an autosomal dominant pattern of inheritance, passing from one generation to the next. Individuals with MODY may experience mild to moderate hyperglycemia, and they can often manage it through lifestyle modifications or oral medications rather than insulin injections. Diagnosis of MODY requires genetic testing to identify the specific gene mutation involved. Understanding the genetic cause of MODY can help guide treatment decisions and provide insight into the risk of diabetes for family members.

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MODY Diabetes: Unraveling the Unique Form of Diabetes

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